Embed Size (px)
Citation preview
Terapia farmacologica nel paziente
obeso-diabetico:
Terapia dell’ipertensione arteriosa
Marco Rossato
Università degli Studi di Padova
Dipartimento di Medicina – DIMED
Clinica Medica 3 Direttore: Prof. Roberto VETTOR
Terapia farmacologica nel paziente obeso-diabetico
Terapia dell’ipertensione arteriosa
> Terapia dell’ipertensione nel soggetto obeso/diabetico
Terapia dell’ipertensione nel soggetto obeso/diabetico
post-chirurgia bariatrica
Obesità
Definizione (WHO)
Condizione caratterizzata da eccessivo peso corporeo per
accumulo di tessuto adiposo, in misura tale da influire
negativamente sullo stato di salute.
Classificazione BMI (kg/m2) Rischio di co-
morbilità
Sottopeso <18.5 Basso (altre
problematiche
cliniche)
Normale 18.5-24.9 Nella media
Sovrappeso 25-29.9 Lieve
Obesità I 30-34.9 Moderato
Obesità II 35-39.9 Grave
Obesità III ≥ 40 Molto grave
Valori pressori che definiscono l’ipertensione arteriosa
Valori pressori arteriosi che definiscono l’ipertensione
Prevalenza dell’obesità (BMI>30 kg m-2)
1960-2025
Epidemiologia dell’obesità/sovrappeso in Italia
50%
18%
24%
34%
22%
37%
0%
10%
20%
30%
40%
50%
60%
Sovrappeso Obesità Obesità addominale
Uomini (n=4908) Donne (n= 4804)
Conseguenze dell’obesità sullo stato di salute:
le conosciamo da molto più tempo di quanto si pensi...
“la morte improvvisa è più frequente nei soggetti obesi che nei soggetti magri”
Ippocrate
cited in Bray, G.A. Endocrinol Metab Clin N. Amer 32 (2003) 787-804
0 20 25 30 35 40 0,0
0,5
1,0
1,5
2,0
2,5
Mort
alit
à
Ris
ch
io r
ela
tivo
BMI
Molto basso
Basso Moderato Alto Molto alto
Relazione tra mortalità e BMI
Bray, J Clin Endocrinol Metab, 1999
L’OBESO “VISCERALE” ha una più alta probabilità
di sviluppare malattie come:
• diabete mellito di tipo 2 (NIDDM)
• dislipidemie
• ipertensione arteriosa
• iperuricemia
• cardiopatia ischemica e ictus
• disturbi respiratori (apnea notturna)
• patologie epatiche
• colecistopatie
• alcune forme di neoplasia
Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome
Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
Kidney disease
Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome
Osteoarthritis
Skin
Gall bladder disease
Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate
Phlebitis venous stasis
Gout
Medical Complications of Obesity
Idiopathic intracranial hypertension
Stroke
Cataracts
Severe pancreatitis
La malattia cardiovascolare resta la
principale causa di morte
395
327
7661 49
326
61
13
452
222
48 39 42 40
5
72
15
0
100
200
300
400
500
Circ.
Tum
ori
Res
p.
Acc
iden
tali G
I
SNC
Mal
. Infe
ttiv
e
Altr
e M
alat
tie
non note
Annuario Statistico Italiano 2001 - ISTAT
Tasso di mortalità (TM)
per 100.000 abitanti in Italia nel 1997
TM
- Epidemiological data unequivocally support the link between body
weight and blood pressure.
- Indeed, greater body weight is one of the major risk factors for high
blood pressure.
- Recent data from NHANES indicate that the prevalence of
hypertension among obese individuals, (BMI > 30 kg/m2), is 42.5%
compared with 27.8% for overweight individuals (BMI 25.0-29.9
kg/m2) and 15.3% for those with BMI < 25 kg/m2.
BMI and Prevalence of Hypertension
Associazione con il rischio di mortalità (RR): Confronto tra l’effetto del BMI, della colesterolemia e della
pressione arteriosa diastolica
2.5
2
1.5
1
0.5
0 20 22 24 26 28 30 32 34 36
RR
Lew EA and Garfinkle L, 1979
BMI (Kg/m ) 2
4
3
2
1
0
5
4
3
2
1
0 150 190 230 270 310 75 85 95 105 115 120
Stamier et al; 1986 Stamier et al; 1978
RR RR
Colesterolemia
(mg%)
Pressione Arteriosa Diastolica (mmHg)
Thirty-two year rates of death due to cardiovascular disease in participants of
the Chicago Heart Association Detection Project in Industry cohort, stratified
by baseline body mass index (BMI) and hypertension (HTN) status
Pathogenesis of Obesity-Related Hypertension
Obesity | VOLUME 21 | NUMBER 1 | JANUARY 2013
Mechanisms by which obesity induces hypertension
Fattori Fisiopatologici
dell’ipertensione arteriosa associata all’obesità
Eccesso di varianti geniche ipertensivanti e/o deficit di varianti genetiche
ipotensivanti
Eccessivo introito di sale con la dieta e deficit escretorio renale
Interazione tra fattori genetici e dieta nello sviluppo dell’ipertensione arteriosa
nell’obeso iperteso
Deficit del sistema natriuretico basato sui peptidi natriuretici cardiaci
Inappropriata accentuazione dell’attività del sistema renina-angiotensina-
aldosterone
Aumentata attività del sistema nervoso simpatico e possibile ruolo della leptina
Insulino-resistenza ed iperinsulinemia
“Disfunzione adipocitaria” e infiammazione cronica basso grado
Terapia dell’ipertensione arteriosa nel soggetto obeso
Prevenzione delle complicanze obesita’
Dieta e Esercizio fisico
Terapia
farmacologica
Chirurgia
bariatrica
Developmental Origins of Obesity-Related Hypertension
The childhood origins of obesity-related hypertension
N Engl J Med 365;20, november 17, 2011
…Overweight or obese children who were obese as adults had increased risks
of type 2 diabetes, hypertension, dyslipidemia, and carotid-artery
atherosclerosis.
The risks of these outcomes among overweight or obese children who became
nonobese by adulthood were similar to those among persons who were never
obese…
Terapia dell’ipertensione arteriosa nel soggetto obeso
Prevenzione delle complicanze obesita’
Dieta e Esercizio fisico
Terapia
farmacologica
Chirurgia
bariatrica
…A diet rich in fruits, vegetables, and low-fat
dairy foods and with reduced saturated and
total fat can substantially lower blood
pressure.
This diet offers an additional nutritional
approach to preventing and treating
hypertension…
Lifestyle Changes in the Management of
Obesity-Related Hypertension
Systematic reviews consistently report a decrease in SBP of about 1 mm Hg
per kg of weight loss with follow-up of 2 to 3 years.
There is attenuation in the longer-term, with a decrease of about 6 mm Hg in
SBP per 10 kg of weight loss.
Intervention programs appropriate for obesity-hypertension combine diet,
physical activity, and behavioral modification and aim to achieve longterm
change in health-related behaviors.
Low-Salt Diets
- Salt sensitivity is commonly associated with obesity. Salt restriction
decreases the risk of hypertension with or without weight loss as well as
reducing the incidence of CV events.
- In the Hypertension Prevention Trial, participants with DBP 78 to 89 mm
Hg were followed for 3 years after being randomized to one of five
groups: control, decreased energy intake, decreased sodium intake,
decreased sodium and energy intake, or decreased sodium and
increased potassium intake.
- BP decreased in all groups of intervenction, with the greatest decrease
in patients assigned to reduced energy only.
- The groups with reduced sodium intake had a significantly lower rate of
hypertension.
Arch Intern Med. 1990;150:153-62
Physical Activity
Aerobic exercise can reduce weight and BP, but when exercise is the only
intervention, weight losses are small, with an estimated change of 1.6 kg in
moderate-intensity programs continued for 6 to 12 months.
In a meta-analysis that included assessment of ambulatory BP it was reported
that in studies lasting 4 to 52 weeks, with physical activity as the only
intervention, aerobic exercise reduced BP by 3/2.4 mm Hg.
The change affected daytime (3.3/3.5 mm Hg) but not nighttime (0.6/1.0 mm
Hg) BP. Clin Exp Pharmacol Physiol. 2006.
The effect on BP was independent of the estimated weight loss of 1.2 kg.
However, when aerobic exercise is combined with calorie restriction for
weight control, the effects on ambulatory BP can be substantial . J Hypertens.
1996.
Alcohol
The pressor effect of alcohol has been established in clinical trials, with an
estimated increase in SBP of 1 mm per 10 g of alcohol .
Paradoxically, drinking alcohol at low to moderate levels is associated with
lower risk of atherosclerotic disease.
Alcohol provides 29 kJ/g and, although weight gain from excess intake might
be expected, meta-analysis has not shown a consistent relationship between
alcohol and weight gain.
In US adults, however, increased alcohol intake was associated with greater
long-term weight gain. Moderation of heavier daily alcohol intake to no more
than one standard drink in women and two standard drinks in men appears
prudent, with potential benefits for both weight gain and BP.
In a factorial trial of independent and combined effects of alcohol moderation
and weight reduction in overweight and obese hypertensive drinkers, effects
on BP were additive over a 3-month period, with the combined modalities
achieving a 14/9 mm Hg BP reduction compared with controls who
maintained usual weight and drinking habits. Hypertension. 1992.
Smoking
Although smokers tend to have lower body weight, they may gain weight
because of clustering of adverse health behaviors .
Smoking increases BP acutely, with an associated rise in arterial stiffness
that lasts longer in hypertensive men.
There is an important window of opportunity for lifestyle programs to
prevent the weight gain (and BP rise) often seen with smoking cessation.
N Engl J Med. 2011
Pressione arteriosa (mmHg)
Altri fattori di rischio, danno
d’organo o riscontro di
patologia concomitante
Normale PAS 120-129 o PAD 80-84
Normale alta PAS 130-139 o PAD 85-89
Grado 1 PAS 140-159 o PAD 90-99
Grado 2 PAS 160-179
o PAD 100-109
Grado 3 PAS > 180
o PAD > 110
Nessun altro fattore di rischio
aggiunto Rischio nella media Rischio nella media
Rischio aggiunto basso
Rischio aggiunto moderato
Rischio aggiunto elevato
1-2 fattori di rischio Rischio aggiunto
basso
Rischio aggiunto
basso
Rischio aggiunto moderato
Rischio aggiunto moderato
Rischio aggiunto molto elevato
3 o più fattori di rischio, SM,
danno d’organo o diabete
Rischio aggiunto moderato
Rischio aggiunto elevato
Rischio aggiunto elevato
Rischio aggiunto elevato
Rischio aggiunto molto elevato
Malattia CV o renale Rischio aggiunto molto
elevato Rischio aggiunto molto
elevato Rischio aggiunto molto
elevato Rischio aggiunto molto
elevato Rischio aggiunto molto
elevato
Trattamento dell’ipertensione arteriosa
Classe di rischio del Paziente facendo riferimento alle Linee guida ESH/ESC
Trattamento dell’ipertensione arteriosa
in relazione alla classe di rischio del paziente facendo riferimento alle linee guida ESH/ESC
As in individuals with diabetes and chronic kidney disease, many
authorities have recommended lower target BPs for obese individuals.
This recommendation is partially due to the constellation of risk factors
associated with obesity and the metabolic syndrome, and is also attributed
to the fact that hypertension in obese patients has proven more difficult to
control than hypertension in the nonobese population. In fact, even modest
weight loss increases the likelihood of achieving goal BPs.
Although logical, there is no strong evidence to support lowering BP much
beyond the defined 140/90 mm Hg threshold .
Treatment of Hypertension in the Obese
BP Thresholds and Targets
Come riportato dalle Linee Guida ESH/ESC del 2013 la maggioranza degli
studi clinici controllati hanno dimostrato che la riduzione significativa
dell’incidenza degli eventi cardiovascolari, nei soggetti affetti da
ipertensione arteriosa, dipendono essenzialmente dalla riduzione degli
elevati valori pressori di per sé, dal raggiungimento del target pressorio e
solo in parte dal tipo di farmaco impiegato.
Ne deriva che i farmaci maggiormente usati a nostra disposizione quali i
diuretici tiazidici (TZ) e tiazidico-simili, i beta-bloccanti (BB), i calcio
antagonisti (CCB), gli ACE inibitori (ACEI) e i bloccanti recettoriali
dell’angiotensina II (ARB o sartani), sono tutti farmaci dotati di un’efficacia
antipertensiva ben documentata.
Terapia anti-ipertensiva nel soggetto obeso iperteso
More than 100 medications are available for the direct treatment of
hypertension, acting on a variety of systems throughout the body.
Although there is no evidence based on longitudinal outcome studies in
obese patients, recommendations for the use of specific antihypertensive
agents in an obese population have emerged.
Antihypertensive Agents
Mechanisms by which obesity induces hypertension
Anti-hypertensive Agents in Obesity
Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers
(ARBs), b-blockers, calcium channel blockers (CCBs), and thiazide diuretics are all
effective in lowering BP in most obese patients. Although lowering BP is of
paramount importance, studies suggest that antagonizing the RAAS system has
special significance in obese patients .
As noted above, angiotensin is overexpressed in obesity, directly contributing to
obesity-related hypertension, making the case to consider ACE inhibitors/ARBs as
first-line agents. In comparison to ARBs or ACE inhibitors, b-blocker- and thiazide-
based regimens increase insulin resistance and are associated with an increase in
new cases of diabetes.
In contrast, regimens based on RAAS inhibition are associated with significantly
fewer cases of new diabetes. This is of particular importance in the obese
population, a group at heightened risk for the development of type 2 diabetes.
In addition, ACE inhibitors and ARBs have not been associated with weight gain or
insulin resistance and provide renal protection in diabetes, a highly prevalent
disease among obese persons.
RAAS Inhibitors
Although thiazide diuretics are often recommended as first-line agents for
the treatment of hypertension, their known dose-related side effects, which
include dyslipidemia and insulin resistance, are undesirable in obese
populations prone to the metabolic syndrome and type 2 diabetes.
This causes a therapeutic dilemma since obesity-related hypertension is
salt-sensitive and diuretics will be required to control BP in most cases.
Many experts recommend low-dose thiazides (12.5 to 25 mg of
hydrochlorothiazide or equivalent agent) along with close lipid and glucose
monitoring.
If greater diuretic effect is required to control BP, the use of loop diuretics
and/or the addition of potassium-sparing agents such as spironolactone,
eplerenone, or amiloride should be considered, given the importance of
aldosterone in obesity-related hypertension.
Diuretics
β-blockers have been shown to cause insulin resistance and have been
closely associated with weight gain and higher body weights, as well as
decreased diet-induced thermogenesis and fat oxidation rate.
The use of β-blockers should be limited to obese patients with specific CV
indications such as postmyocardial infarction and heart failure. When β-
blockers are indicated, agents with a vasodilating component such as
carvedilol and nebivolol appear to have less weight gain potential and less
of an impact on carbohydrate and lipid metabolism.
Although appropriate in heart failure, the protective effect of these agents
with vasodilator effects postmyocardial infarction has not been definitively
established
β-blockers
Calcium channel blockers are also effective in the treatment of obesity
related hypertension and have not been associated with weight gain or
adverse changes in lipids.
Calcium channel blockers
Treatment of resistant hypertension in obese patients
Data on how to treat obese patients with resistant arterial hypertension are
scarce. In these patients, adding the mineralocorticoid antagonist spironolactone
may be useful (in doses of 25 – 100 mg/day).
Remarkably, higher waist circumference has been associated with better response
to spironolactone. These findings point to the special role of aldosterone in
obesity- associated hypertension. Direct renin inhibition (aliskiren) may be an
effective alternative treatment approach in obese hypertensive patients. However,
the medication should be used with caution, particularly in combination with
other renin – angiotensin system inhibitors or renal disease.
Recently, a large outcomes study testing aliskiren in combination with either
angiotensin receptor blockade or angiotensin-converting enzyme inhibition in
high-risk patients with diabetes mellitus was prematurely discontinued due to
severe adverse effects.
Given the important role of the sympathetic nervous system in the
pathogenesis of obesity-associated arterial hypertension and insulin
resistance, central sympatholytic drugs are another treatment option for
patients not responding to or not tolerating first-line antihypertensive
drugs.
Treatment of resistant hypertension in obese patients
Renal sympathetic denervation through a novel catheter-based approach
substantially reduced blood pressure in patients with treatment-resistant
arterial hypertension with an average BMI of 31kg/m. The response may be
mediated in part through ablation of renal afferent nerves decreasing centrally
generated sympathetic activity. Renal sympathetic denervation may also
improve glucose metabolism.
Another device-based approach is electrical baroreflex activation. The
treatment requires surgical implantation of a pacemaker device and
electrodes located at the level of the carotid sinus. Baroreflex activation
therapy reduces blood pressure through sympathetic inhibition.
In a recent controlled clinical trial including treatment-resistant hypertensive
patients with an average BMI of 32.4kg/m2, baroreflex activation therapy did
not increase the proportion of patients achieving an at least 10 mmHg
reduction in systolic blood pressure at month 6 (primary endpoint). However,
the treatment increased the likelihood of achieving blood pressure control and
showed promising effects on long-term blood pressure control. Clearly, both
treatments need to be tested in larger clinical trials with hard endpoints.
Treatment of resistant hypertension in obese patients
Potential targets of drug treatments to improve
vascular reactivity in patients with diabesity
Bariatric drugs
Bariatric surgeries affect or restrict the flow of food through the
gastrointestinal tract. Restrictive surgical procedures, such as laparoscopic-
adjustable gastric banding (LAGB), induce earlier satiety by decreasing the
volume of the stomach. The Roux-en-Y gastric bypass (RYGB) involves both
restriction of the stomach and bypass of the small bowel. The sleeve
gastrectomy, in which the fundus of the stomach is removed, is becoming
increasingly popular. However, RYGB and LAGB remain the most broadly
used surgical treatments for morbid obesity and associated conditions,
including obesity-related hypertension .
In an extensive meta-analysis of 136 studies, Buchwald and colleagues
evaluated the impact of bariatric surgery on weight loss and obesity-related
comorbidities including diabetes and hypertension.
The mean percentage of excess weight loss was 61.2% for all patients.
Diabetes resolved in 76.8% of patients and resolved or improved in 86.0%,
whereas hypertension resolved in 61.7% of patients and resolved or
improved in 78.5%.
Bariatric surgery
…In recent years, surgeons have been unexpectedly challenging physicians in the treatment of diabesity….
Mingrone et al, NEJM, 2012
0% 75% 95%
Brethauer et al., 2013
Buchwald H et al, JAMA, 2004
…Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement…
Figure. Forest plot of mean differences in weight and diastolic and systolic blood pressure at follow-up of at least 2 years.
Aucott L et al. Hypertension 2009;54:756-762
Copyright © American Heart Association, Inc. All rights reserved.
Factors associated with the resolution of hypertension
following Roux-en-Y gastric bypass
Bland CM, Am J Health-Syst Pharma, 2013
…Patients experience progressive and drastic reduction of the dose of
anti-hypertensive agents after sleeve gastrectomy…
….Literature regarding medication adjustment strategies and outcomes
for bariatric patients is limited, especially for sleeve gastrectomy
patients. Hypoglycemia in the acute postoperative period is well
described for RYGB patients while data for sleeve gastrectomy patients
are limited. Hypotension is also a concern, as many patients take
multiple antihypertensives preoperatively and have limited fluid intake in
the immediate postoperative period. Patients in the early postoperative
period have difficulty adhering to fluid goals, which increases the risk for
dehydration and hypotension…..
Bland CM, Am J Health-Syst Pharma, 2013
Treatment of hypertension in obese patients
after bariatric surgery (1)
…When adjustments to antihypertensive medications are necessary,
diuretics should be the first medication class to be withheld to limit volume
depletion and hypotension after surgery.
Beta-blockers were continued after surgery for perioperative b-blockade….
Bland CM, Am J Health-Syst Pharma, 2013
Treatment of hypertension in obese patients
after bariatric surgery (2)
L’IPERTENSIONE ARTERIOSA NEL PAZIENTE OBESO
Raccomandazioni Congiunte
della Società Italiana Ipertensione Arteriosa (SIIA)
e della Società Italiana Obesità (SIO)
2014
Riccardo Sarzani, Cesare Cuspidi, Maurizio Castellano, Ferruccio Galletti, Anna
Maria Grandi, Lelio Morricone, Fabrizio Pasanisi, Marco Rossato, Guido Salvetti
a nome dei comitati direttivi della SIIA e della SIO
- Obesity-related hypertension is an important public health issue.
- As the prevalence of obesity increases, the prevalence of hypertension
with its associated CV risk will increase as well.
- While primary and even primordial prevention is the long-term goal for
diminishing the prevalence of obesity, control of both obesity and
hypertension in the population at risk is the overriding current challenge.
- Treating hypertension in the obese requires addressing the obesity as
part of the therapeutic plan.
- Lifestyle management is required in every case, with a focus on weight
loss and risk reduction. Some have likened the treatment of obesity with
caloric restriction alone to the treatment of hypertension with sodium
restriction: it works if extreme enough, but it is not a feasible long-term
strategy.
- In most patients, additional therapies including medications, aggressive
diet counseling and behavioral techniques, and sometimes bariatric
surgery will be required.
Conclusions
…bariatric surgery cannot be considered a universal panacea
due to some serious shortcomings, such as the requirement
for specialist surgeons and a not-inconsiderable perioperative
mortality, are driving researchers to investigate the prospects
for new treatments to provide the desired effects without
operative risks….
Cardillo C, Ann Pharm Fr, 2012
Timeo chirurgos et dona ferentes ! Prof. Antonio Girolami, 1984, CdL M&C, III-IV a, Patologia Speciale Medica
Pieter Claesz. Soutman (1593/1601) - Laocoön and his sons being strangled by serpents
Non timeo chirurgos quia dona ferentes
…nonnumquam ! 2014,Incontro Congiunto SICOb – SID - SIO
Pieter Claesz. Soutman (1593/1601) - Laocoön and his sons being strangled by serpents
Obesity and Stroke
Hypertension and Stroke
Obesity and Hypertension
Prevalence
– 35% of obese have hpt
– 17% of desirable BMI have hpt
Diagnostic Criteria – systolic BP > 140 or
– diastolic BP > 90
2009
Hypertension The Dangers
The heart to get larger, which may lead to heart failure.
Small bulges (aneurysms) to form in blood vessels.
Blood vessels in the kidney to narrow, which may lead to kidney failure.
Arteries in the body to harden faster, especially those in the
heart, brain, kidneys, and legs. This can cause a heart attack, stroke,
kidney failure, or can lead to amputation of part of the extremities.
Blood vessels in the eye to burst or bleed. This may cause
vision changes and can result in blindness.
Failure to find and treat HTN is serious, as untreated HTN can cause:
NHLBI
2009
Hypertension
Blood pressure is often increased in overweight individuals.
Estimates suggest that control of overweight would eliminate 48%
of the hypertension in Caucasians and 28% in African Americans.
Overweight and hypertension interact with cardiac
function, leading to thickening of the ventricular
wall and larger heart volume, and thus to a
greater likelihood of cardiac failure.
J La State Med Soc .2005; 157 (1): S42-49.
TOD: danno d’organo bersaglio – CCA: condizioni cliniche associate – AGG.: aggiuntivo alla pressione
RISCHIO
AGGIUNTIVO
MOLTO
ELEVATO
RISCHIO
AGGIUNTIVO
MOLTO
ELEVATO
RISCHIO
AGGIUNTIVO
MOLTO
ELEVATO
RISCHIO
AGGIUNTIVO
MOLTO ELEVATO
RISCHIO
AGGIUNTIVO
ELEVATO
IV. CCA
RISCHIO
AGGIUNTIVO
MOLTO
ELEVATO
RISCHIO
AGGIUNTIVO
ELEVATO
RISCHIO
AGGIUNTIVO
ELEVATO
RISCHIO
AGGIUNTIVO
ELEVATO
RISCHIO
AGGIUNTIVO
MODERATO
III. 3 o piu’ fattori di
rischio o TOD o
diabete
RISCHIO
AGGIUNTIVO
MOLTO
ELEVATO
RISCHIO
AGGIUNTIVO
MODERATO
RISCHIO
AGGIUNTIVO
MODERATO
RISCHIO
AGGIUNTIVO
BASSO
RISCHIO
AGGIUNTIVO
BASSO
II. 1-2 fattori di
rischio
RISCHIO
AGGIUNTIVO
ELEVATO
RISCHIO
AGGIUNTIVO
MODERATO
RISCHIO
AGGIUNTIVO
BASSO
RISCHIO NELLA
MEDIA
RISCHIO NELLA
MEDIA I. Nessun fattore di
rischio aggiunto
Grado III
PAS ≧ 180
PAD ≧ 110
Grado II
PAS 160-179
PAD 100-109
Grado I
PAS 140-159
PAD 90-99
Normale-alta
PAS 130-139
PAD 85-89
Normale
PAS 120-129
PAD 80-84
PRESSIONE ARTERIOSA Altri fattori di
rischio o
riscontro di
malattia
STRATIFICAZIONE DEL RISCHIO
ESH-ESC 2003
J Hypertension 2003,21:1011-1053
35%
65%
IPERTESI NORMOTESI
PRESSIONE ARTERIOSA NORMALE:
<140/90 MM HG
Eziopatogenesi dell’Obesità
Fattori ambientali Comportamentali
30%
Fattori Genetici 70%
Influenze ambientali
Fattori psicologici
Fattori sociologici
Fattori religiosi
Appetibilità del cibo
Fattori ormonali
Fattori metabolici
Fattori nervosi
OBESITA’ Malattia multifattoriale
Salt sensitivity is commonly associated with obesity. Salt restriction decreases the risk of hypertension with or
without weight loss as well as reducing the incidence of CV events. In the Hypertension Prevention Trial,
participants with DBP 78 to 89 mm Hg were followed for 3 years after being randomized to one of five groups:
control, decreased energy intake, decreased sodium intake, decreased sodium and energy intake, or
decreased sodium and increased potassium intake. BP decreased in all groups, with the greatest decrease in
patients assigned to reduced energy only. The groups with reduced sodium intake had a significantly lower
rate of hypertension. Arch Intern Med. 1990.
In the Trials of Hypertension Prevention (TOHP) phase I study, (135) participants with high normal BP
were randomized to one of four groups for 18 months: control, weight loss, sodium restriction, or stress
management. In the weight reduction group, weight decreased by 3.9 kg and BP by 2.9/2.3 mm Hg. Sodium
restriction resulted in a decrease in BP of 1.7/2.9 mm Hg. Seven years later, the odds ratio for hypertension
among 181 participants was lower by 77% with weight loss and 35% with sodium restriction. Am J Clin Nutr.
1997.
Phase II of TOHP examined the effects of weight loss, sodium restriction, or both on BP and the incidence of
hypertension (136(137). At 6, 18, and 36 months, weight loss favored the weight reduction intervention over
usual care, although weight loss was attenuated over time, and change in BP showed a similar pattern. In the
sodium reduction group, a decrease in BP was greater at each time point and also became attenuated with
time, from 5.1/4.4 mm Hg at 6 months to 0.7/3.0 mm Hg at 3 years. Ann Intern Med. 2001.
The Trial of Nonpharmacologic Interventions in the Elderly (TONE) study (138) investigated weight loss
and salt restriction and the need for antihypertensive drugs in treated hypertensive patients during follow-up to
a median of 29 months. Weight reduction, sodium restriction, and the combination of both were compared with
usual care in obese participants. The relative hazard ratio was 0.60 for reduced sodium alone, 0.64 for weight
loss alone, and 0.47 for the combined intervention. The within-groups rate of adverse events was similar.
Arch Intern Med 2001
Low-Salt Diets
Long-Term Effects of Lifestyle
Although limited data are available, a few interventions and meta-analyses
report long-term benefits associated with improvements in lifestyle,
especially in at-risk populations.
In 10- to 15-year follow-up of prehypertensive adults who took part in the
TONE studies, the risk of a CV event was lower by 25% to 30% in those who
had been assigned to the salt-restricted group.
In adults at risk for diabetes, a program of diet and physical activity reduced
the risk of diabetes by 58%, with size of the decrease related to the extent of
change in lifestyle.
In adults with impaired glucose tolerance, a program of diet and physical
activity was more effective for the prevention of diabetes than either
metformin or usual care, with respective incidence rates per 100 person-
years of 4.8, 7.8, and 11.
As hypertension progresses, the risk of death from ischemic heart disease
or stroke (beginning with a normal BP of 115/75 mm Hg) doubles with each
increment of 20 mm Hg in SBP or 10 mm Hg in DBP across the entire BP
range from 115/75 mm Hg to 185/115 mm Hg.
Individuals in the general population with a SBP of 120 to 139 mm Hg or a
DBP of 80 to 89 mm Hg are considered prehypertensive and require lifestyle
modification to prevent CVD. Patients with prehypertension are at twice the
risk of developing hypertension as those with normal BP.
Stage 1 hypertension is defined as SBP between 140 and 159 mm Hg or
DBP between 90 and 99 mm Hg.
Stage 2 hypertension is defined as SBP 160 mm Hg or DBP 100 mm Hg.
To reduce the incidence of CV and renal complications, target BPs for the
general population should be <140/90 mm Hg and for patients with
established diabetes or chronic kidney disease <130/80 mm Hg, but there is
limited evidence in support of this lower threshold.
Treatment of Hypertension in the Obese
BP Thresholds and Targets (1)
20 21 22 23 24 25 26 27 28 29 30 0
1
2
3
4
5
6 R
ischio
rela
tivo
BMI
Diabete tipo 2
Ipertensione
Colelitiasi
Coronaropatie
Relazione tra BMI e rischio relativo di: DIABETE TIPO 2, IPERTENSIONE, COLELITIASI E CORONAROPATIE
Willet et al, N Engl J Med, 1999
Predicted 10-year risk for hard coronary heart disease events
for a 50-year-old man with selected levels of risk factors
and blood pressure (BP) stages
